In the November issue of the Journal, Wolff et al. diligently researched the subject of sex-specific outcomes of COVID-19 by enrolling patients ≥ 70 yr old from the multicentre COVIP database.1 While model 2 showed a significantly higher need for tracheostomy and renal replacement therapy and a higher 30-day mortality in the male cohort than in the female cohort, the statistically significant difference in mortality was lost in model 3 after adjusting for treatment limitations in the index multilevel regression analysis.1

Nonetheless, Wolff et al. did not account for the concurrent thrombotic complications, which increase the risk of COVID-19-related mortality.2 Thrombotic complications are pertinent to the comparative research by Wolff et al. because independent researchers like the CLOT-COVID investigators have suggested that men with COVID-19 develop thrombosis more often than women with COVID-19 do.1, 3

Sex-specific outcomes are also dependent on age in the critically ill, as hinted in the French and European Outcome Registry in Intensive Care Units (FROG-ICU) study.4 Having said that, the sex-related differences in the risk of thrombosis would have been even more interesting to witness in the Wolff et al. analysis, given the authors included an exclusive elderly cohort of individuals ≥ 70 yr of age. This assumes an enhanced importance in the light of the Wilcox et al. findings, which outlined an attenuating effect of age on the male sex associated elevated thrombosis risk in a retrospective evaluation of 3,334 COVID-19 patients in a large New York health system.2 Simultaneously, the lack of assessment of obesity as a comorbidity and the changing standard of care (including pharmacotherapy) may have further compounded the matter of thrombotic complications in the Wolff et al. study.

Lastly, Mukhopadhyay et al. very recently delineated a stronger association of peak D-dimer with severe COVID-19 illness in males than in females (OR, 2.91; 95% CI, 2.63 to 3.24 vs OR, 2.31; 95% CI, 2.04 to 2.63; P interaction = 0.005), which further buttresses the relevance of the entire discussion pertaining to sex-specific thrombosis risk in COVID-19.5